The specific goals of the research project are: 1) to define and quantitate fetal compensatory mechanisms during reduced uterine blood flow in the chronically hypoxic fetal preparation, and 2) to identify and correlate the physiologic, metabolic, electroencephalographic, and neuropathologic observations associated with chronic fetal hypoxia. Using the chronically instrumented sheep preparation with placental vascular insufficiency, various fetal physiologic and metabolic observations will be assessed and correlated with observations of brain function in terms of EEG and brain structure as reflected by neuropathologic evaluation. Placental vascular insufficiency will be created by microsphere embolization of the uterine circulation. The parameters measured will be uterine and umbilical blood flow and maternal and fetal pH, pO2, pCO2, glucose, lactate and pyruvate. From this data fetal glucose uptake and fetal aerobic and anaerobic metabolic rate will be calculated. Brain function will be evaluated by the fetal electroencephalogram, and brain neuropathology by conventional light and electron microscopic examination if indicated. The experimental animals will be divided into six groups. Group I will be those animals showing evidence of persistent fetal acidosis following surgical preparation. Group II will be animals where measurements will be obtained after two days of chronic hypoxia induced by the placental insufficiency. Groups III through VI will be animals in whom measurements will be obtained initially after two days of chronic hypoxia secondary to placental insufficiency and again during graded superimposed acute hypoxia produced by a reduction in uterine blood flow as a result of continuous maternal epinephrine infusion. In all Groups the fetuses will be sacrificed for neuropathologic examination. The health-related implications lie clearly in improving our understanding of the pathophysiology and fetal effects of chronic fetal hypoxia.